Push or pull: how cytoskeletal crosstalk facilitates nuclear movement through 3D environments

As cells move from two-dimensional (2D) surfaces into complex 3D environments, the nucleus becomes a barrier to movement due to its size and rigidity. Therefore, moving the nucleus is a key step in 3D cell migration. In this review, we discuss how coordination between cytoskeletal and nucleoskeletal networks is required to pull the nucleus forward through complex 3D spaces. We summarize recent migration models which utilize unique molecular crosstalk to drive nuclear migration through different 3D environments. In addition, we speculate about the role of proteins that indirectly crosslink cytoskeletal networks and the role of 3D focal adhesions and how these protein complexes may drive 3D nuclear migration.

The Enteric Nervous System and the Microenvironment of the Gut: The Translational Aspects of the Microbiome-Gut-Brain Axis

The proper functioning of the gastrointestinal tract is essential for digestion, absorption and the elimination of waste products. It protects us against pathogens, allergens and toxins, continuously monitoring and regulating the internal environment. The vast majority of these tasks are carried out by the nervous and immune systems of the gut in close cooperation by constantly adapting to internal and external stimuli, maintaining its homeostasis. In this review, we would like to summarize the most recent findings about the cytoarchitecture and functional microanatomy of the enteric nervous system and the immune microenvironment of the gut highlighting the essential role and inevitable molecular crosstalk between these two highly organized networks. Gut neuroimmunology is a rapidly evolving field and might help us to understand the etiology of inflammatory bowel disease and the systemic consequences of chronic intestinal inflammation. Finally, we also included a brief outlook to present the most recent research depicting the multifaceted role of the gut microbiome, its contribution to the gut-brain axis and human disease.

Vascular proteome responses precede organ dysfunction in sepsis

Vascular dysfunction and organ failure are two distinct, albeit highly interconnected clinical outcomes linked to morbidity and mortality in human sepsis. The mechanisms driving vascular and parenchymal damage are dynamic and display significant molecular crosstalk between organs and tissues. Therefore, assessing their individual contribution to disease progression is technically challenging. Here, we hypothesize that dysregulated vascular responses predispose the organism to organ failure. To address this hypothesis, we have evaluated four major organs in a murine model of S. aureus sepsis by combining in vivo labeling of the endothelial proteome, data-independent acquisition (DIA) mass spectrometry, and an integrative computational pipeline. The data reveal, with unprecedented depth and throughput, that a septic insult evokes organ-specific proteome responses that are highly compartmentalized, synchronously coordinated, and significantly correlated with the progression of the disease. Vascular proteome changes were found to precede bacterial invasion and leukocyte infiltration into the organs, as well as to precede changes in various well-established cellular and biochemical correlates of systemic coagulopathy and tissue dysfunction. Importantly, our data suggests a potential role for the vascular proteome as a determinant of the susceptibility of the organs to undergo failure during sepsis.

The Hepatic Stellate Cells (HSTCs) and Adipose-derived Mesenchymal Stem Cells (ASCs) Axis as a Potential Major Driver of Metabolic Syndrome – Novel Concept and Therapeutic Implications

Herein, we would like to introduce a novel concept for the prevention and treatment of metabolic syndrome, which is based on molecular relationship between liver and adipose tissue. Particularly, we believe, that unravelling the molecular crosstalk between hepatokines and adipokines will allow to better understand the pathophysiology of metabolic diseases and allow to develop novel, effective therapeutic solutions against obesity and metabolic syndrome. Graphical Abstract Inter-organ communication on the level of stem progenitor cells-hepatic stellate cells (HSTCs) and adipose-derived progenitors (ASCs) could represents a key mechanism involved in controlling glucose tolerance as well as insulin sensitivity.

Functional Intricacy and Symmetry of Long Non-Coding RNAs in Parasitic Infections

RNAs are a class of molecules and the majority in eukaryotes are arbitrarily termed non- coding transcripts which are broadly classified as short and long non-coding RNAs. Recently, knowledge of the identification and functions of long non-coding RNAs have continued to accumulate and they are being recognized as important molecules that regulate parasite-host interface, parasite differentiation, host responses, and disease progression. Herein, we present and integrate the functions of host and parasite long non-coding RNAs during infections within the context of epigenetic re-programming and molecular crosstalk in the course of host-parasite interactions. Also, the modular range of parasite and host long non-coding RNAs in coordinated parasite developmental changes and host immune dynamic landscapes are discussed. We equally canvass the prospects of long non-coding RNAs in disease diagnosis and prognosis. Hindsight and suggestions are offered with the aim that it will bolster our understanding for future works on host and parasite long non-coding RNAs.

Fusion with Promiscuous Gα16 Subunit Reveals Signaling Bias at Muscarinic Receptors

A complex evaluation of agonist bias at G-protein coupled receptors at the level of G-protein classes and isoforms including non-preferential ones is essential for advanced agonist screening and drug development. Molecular crosstalk in downstream signaling and a lack of sufficiently sensitive and selective methods to study direct coupling with G-protein of interest complicates this analysis. We performed binding and functional analysis of 11 structurally different agonists on prepared fusion proteins of individual subtypes of muscarinic receptors and non-canonical promiscuous α-subunit of G16 protein to study agonist bias. We have demonstrated that fusion of muscarinic receptors with Gα16 limits access of other competitive Gα subunits to the receptor, and thus enables us to study activation of Gα16 mediated pathway more specifically. Our data demonstrated agonist-specific activation of G16 pathway among individual subtypes of muscarinic receptors and revealed signaling bias of oxotremorine towards Gα16 pathway at the M2 receptor and at the same time impaired Gα16 signaling of iperoxo at M5 receptors. Our data have shown that fusion proteins of muscarinic receptors with α-subunit of G-proteins can serve as a suitable tool for studying agonist bias, especially at non-preferential pathways.

Crosstalk between Light- and Temperature-Mediated Processes under Cold and Heat Stress Conditions in Plants

Extreme temperatures are among the most important stressors limiting plant growth and development. Results indicate that light substantially influences the acclimation processes to both low and high temperatures, and it may affect the level of stress injury. The interaction between light and temperature in the regulation of stress acclimation mechanisms is complex, and both light intensity and spectral composition play an important role. Higher light intensities may lead to overexcitation of the photosynthetic electron transport chain; while different wavelengths may act through different photoreceptors. These may induce various stress signalling processes, leading to regulation of stomatal movement, antioxidant and osmoregulation capacities, hormonal actions, and other stress-related pathways. In recent years, we have significantly expanded our knowledge in both light and temperature sensing and signalling. The present review provides a synthesis of results for understanding how light influences the acclimation of plants to extreme low or high temperatures, including the sensing mechanisms and molecular crosstalk processes.

Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol’s family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.

MicroRNAs and Oxidative Stress: An Intriguing Crosstalk to Be Exploited in the Management of Type 2 Diabetes

Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target.